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Abstract Context Bone mineral density (BMD) T-score references may be updated when the peak BMD of the population is unclear and warrants reevaluation. Objective To update BMD T-score references using the peak BMD from the most recent National Health and Nutrition Examination Survey (NHANES) data. Methods This cross-sectional study used NHANES data from 2005 to 2014. Non-Hispanic White females between the ages of 10 and 40 years (N = 1549) were our target population to estimate peak BMD (SD). Individuals aged ≥ 50 years (N = 5523) were used to compare the percentages of osteoporosis and low bone mass based on existing and updated BMD T-score references. BMD data within the age at attainment of peak BMD ± 5 years were used to calculate updated BMD T-score references. Results The updated average of BMD (SD) for diagnosing osteoporosis at the femoral neck and lumbar spine were 0.888 g/cm2 (0.121 g/cm2) and 1.065 g/cm2 (0.122 g/cm2), respectively. The percentages of individuals with osteoporosis at the femoral neck and low bone mass at the femoral neck and lumbar spine based on the updated BMD T-score references were higher than the percentages of people designated with these outcomes under the existing guidelines (P < 0.001). However, we observed the opposite pattern for lumbar spine osteoporosis (P < 0.001). Conclusions We calculated new BMD T-score references at the femoral neck and lumbar spine. We found significant differences in the percentages of individuals classified as having osteoporosis and low bone mass between the updated and existing BMD T-score references.

Summary We investigated the efficacy of romosozumab in premenopausal women with low bone mass. Romosozumab substantially increased bone mineral density and trabecular bone score in these women, aligning with its proven therapeutic benefits for postmenopausal osteoporosis. Purpose Romosozumab, an anti-sclerostin antibody, is a promising anabolic agent that increases bone formation and decreases bone resorption. However, its efficacy in premenopausal women with low bone mass remains understudied. Methods We retrospectively reviewed premenopausal women with low bone mass treated with romosozumab (ROMO group) or drug-naïve patients (control group). Patients in the ROMO group were classified into the glucocorticoid-induced osteoporosis (GIOP), idiopathic osteoporosis (IOP), and pregnancy and lactation-induced osteoporosis (PLO) subgroups. Bone mineral density (BMD) and trabecular bone score (TBS) were measured before and after one year of romosozumab treatment. Results Twenty-five patients in the ROMO group and five in the control group were included in the study. Among patients in the ROMO group, 12 were in the GIOP, 9 in the IOP, and 4 in the PLO subgroups. The mean age was 37.0 years [32.0–42.0], and the median body mass index was 18.8 kg/m 2 [17.5–21.3]. After romosozumab treatment, lumbar spine (LS), femur neck (FN) BMD, and TBS increased from baseline (LSBMD, 12.8% [8.2–19.3], p  < 0.001; FNBMD, 4.6% [− 0.6–10.7], p  = 0.016; TBS, 4.1% ± 3.8, p  < 0.001) in the ROMO group. Patients in both the GIOP and IOP subgroups showed a significant increase in LSBMD, while those in the IOP subgroup demonstrated significant increases in FNBMD. Conclusion We demonstrated romosozumab’s efficacy in BMD increment in premenopausal women. Romosozumab may be a potential treatment option for premenopausal women with low bone mass, regardless of etiologies, although further research on fracture risk reduction is warranted.

PurposeThis randomized controlled trial compared changes in bone mineral density (BMD) and bone turnover in postmenopausal women with low bone mass randomized to 12 months of either risedronate, exercise, or a control group.MethodsTwo hundred seventy-six women with low bone mass, within 6 years of menopause, were included in analysis. Treatment groups were 12 months of (a) calcium and vitamin D supplements (CaD) (control), (b) risedronate + CaD (risedronate), or (c) bone-loading exercises + CaD (exercise). BMD and serum markers for bone formation (Alkphase B) and resorption (Serum Ntx) were analyzed at baseline, 6, and 12 months.ResultsUsing hierarchical linear modeling, a group by time interaction was found for BMD at the spine, indicating a greater improvement in the risedronate group compared to exercise (p ≤ .010) or control groups (p ≤ .001). At 12 months, for women prescribed risedronate, changes in BMD at the spine, hip, and femoral neck from baseline were + 1.9%, + 0.9%, and + .09%; in exercise group women, + 0.2%, + 0.5%, and − 0.4%; and in control group women, − 0.7%, + 0.5%, and − 0.5%. There were also significant differences in reductions in Alkphase B (RvsE, p < .001, RvsC, p < .001) and Serum Ntx (RvsE, p = .004, RvsC, p = .007) in risedronate women compared to exercise and control groups. For risedronate, 12-month changes in Alkphase B and Serum Ntx were − 20.3% and − 19.0%; for exercise, − 6.7% and − 7.0%; and for control, − 6.3% and − 9.0%.ConclusionPostmenopausal women with low bone mass should obtain adequate calcium and vitamin D and participate in bone-loading exercises. Additional use of BPs will increase BMD, especially at the spine.

Summary Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5 . Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient. Purpose Low-density lipoprotein receptor-related protein 5 ( LRP5 ) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases. Methods Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress. Results Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment. On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up. Conclusion This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study.

A 29-year-old Spanish Caucasian man, without relevant family history, was attended in our unit due to an undiagnosed skeletal dysplasia associated with low bone mass and several fragility fractures throughout his childhood and adolescence. DXA exams throughout his life showed very low BMD values; currently, his spinal and femoral neck T-scores were − 4.3 and − 3.5, respectively. Blood and urinary tests were normal. Other relevant features included right hand and foot syndactyly, aplasia cutis, right hemibody hypoplasia, vertebral malformations, abnormal-looking humerii, and Asperger’s syndrome among others. Whole exome sequencing retrieved a highly probable pathogenic variant in the PORCN gene p.(Arg296Pro) in mosaicism. PORCN mutations cause focal dermal hypoplasia (FDH), an X-linked ultra-rare ecto-mesodermal disorder characterized by several of the findings the patient presented. However, low BMD has not been classically associated with the disease. Noteworthy, PORCN is key for canonical Wnt signaling. Literature scrutiny has yielded other cases of FDH with skeletal fragility during childhood. In addition, preclinical studies with PORCN inhibitors, currently under development as an antitumoral therapy, have shown rapid detrimental effects on bone mass. Collectively, these findings indicate that FDH is probably an underrecognized monogenic cause of low bone mass due to defective Wnt signaling.

Bone health problem is one of the important concomitant diseases of breast cancer (BC). This study aimed to investigate the bone health status of newly diagnosed female BC patients in China. A total of 636 newly diagnosed female BC patients and 268 women undergoing routine physical examinations (control group) were included. Bone mineral density and bone metabolism parameters were assessed. The association between BC and abnormal bone mass (ABM) was analyzed by logistic regression. We found that approximately 15.3% of BC patients presented with hypocalcemia after albumin adjustment. 25-OHVitD deficiency or insufficiency was observed in 92.3% of BC patients. ABM was identified in 63.2% of BC patients, comprising 36.4% with osteopenia and 26.8% with osteoporosis. ABM prevalence was significantly higher in BC patients under 40 years old (40.8%) compared to 8% in the age-matched control group. The severity of bone loss correlated with elevated bone turnover markers. Logistic regression analysis showed that a 5.5-fold and 3.4-fold increased risk of ABM and osteoporosis, respectively, in newly diagnosed BC patients versus the control group. All BC subtypes were associated with a markedly higher risk of ABM. Young BC patients (< 45 years) exhibited a nearly 9-fold higher risk of ABM compared to their age-matched counterparts. Vitamin D deficiency/insufficiency, osteopenia, and osteoporosis were highly prevalent among newly diagnosed female BC patients. Regardless of age and BC subtype, BC patients face a higher risk of ABM compared to those physical examination women, especially among the young.

Purpose To assess bone mineral density (BMD) in middle-aged individuals in Shanghai, in order to improve awareness of osteopenia and osteoporosis screening. Methods The clinical data of 1107 permanent residents of Shanghai aged 40–60 years were collected using a random cluster sampling method. Osteoporosis questionnaire survey and BMD test were conducted. Mann-Whitney U and Chi-square test were used to compare sex, age and body mass index at different stages of bone mass, and Pearson test was used to conduct correlation analysis. Logistic regression was used to analyze the influencing factors. Results The detection rates of osteopenia and osteoporosis were 59% and 12.5% respectively, and bone mineral density was correlated with sex, age, and body mass index ( P  < 0.05). Conclusion The incidence of low bone mass is high in the assessed population, screening for low bone mass should be actively carried out to improve public awareness. It is also good for public health management. Registered clinical trial The trial was approved by Chinese Clinical Trial Registry on February 11, 2021(ChiCTR2100043369).

Abstract Context Osteopathia striata with cranial sclerosis (OSCS) is a rare bone disorder with X-linked dominant inheritance, characterized by a generalized hyperostosis in the skull and long bones and typical metaphyseal striations in the long bones. So far, loss-of-function variants in AMER1 (also known as WTX or FAM123B), encoding the APC membrane recruitment protein 1 (AMER1), have been described as the only molecular cause for OSCS. AMER1 promotes the degradation of β-catenin via AXIN stabilization, acting as a negative regulator of the WNT/β-catenin signaling pathway, a central pathway in bone formation. Objective In this study, we describe a Dutch adult woman with an OSCS-like phenotype, namely, generalized high bone mass and characteristic metaphyseal striations, but no genetic variant affecting AMER1. Results Whole exome sequencing led to the identification of a mosaic missense variant (c.876A > C; p.Lys292Asn) in CTNNB1, coding for β-catenin. The variant disrupts an amino acid known to be crucial for interaction with AXIN, a key factor in the β-catenin destruction complex. Western blotting experiments demonstrate that the p.Lys292Asn variant does not significantly affect the β-catenin phosphorylation status, and hence stability in the cytoplasm. Additionally, luciferase reporter assays were performed to investigate the effect of p.Lys292Asn β-catenin on canonical WNT signaling. These studies indicate an average 70-fold increase in canonical WNT signaling activity by p.Lys292Asn β-catenin. Conclusion In conclusion, this study indicates that somatic variants in the CTNNB1 gene could explain the pathogenesis of unsolved cases of osteopathia striata.

This study aimed to assess the diagnostic accuracy of radiomics for predicting osteoporosis and the quality of radiomic studies. The study protocol was prospectively registered on PROSPERO (CRD42023425058). We searched PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to June 1, 2023, for eligible articles that applied radiomic techniques to diagnosing osteoporosis or abnormal bone mass. Quality and risk of bias of the included studies were evaluated with radiomics quality score (RQS), METhodological RadiomICs Score (METRICS), and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tools. The data analysis utilized the R program with mada, metafor, and meta packages. Ten retrospective studies with 5926 participants were included in the systematic review and meta-analysis. The overall risk of bias and applicability concerns for each domain of the studies were rated as low, except for one study which was considered to have a high risk of flow and time bias. The mean METRICS score was 70.1% (range 49.6–83.2%). There was moderate heterogeneity across studies and meta-regression identified sources of heterogeneity in the data, including imaging modality, feature selection method, and classifier. The pooled diagnostic odds ratio (DOR) under the bivariate random effects model across the studies was 57.22 (95% CI 27.62–118.52). The pooled sensitivity and specificity were 87% (95% CI 81–92%) and 87% (95% CI 77–93%), respectively. The area under the summary receiver operating characteristic curve (AUC) of the radiomic models was 0.94 (range 0.8 to 0.98). The results supported that the radiomic techniques had good accuracy in diagnosing osteoporosis or abnormal bone mass. The application of radiomics in osteoporosis diagnosis needs to be further confirmed by more prospective studies with rigorous adherence to existing guidelines and multicenter validation.

Osteoporosis and osteopenia, collectively referred to as Low Bone Mass Disorders (LBMD), are characterized by decreased bone density and increased fracture risk. Studies have identified a potential link between cardiovascular disease and LBMD, and the role of lipid metabolism in this has attracted widespread attention. We analyzed participant information collected from multiple NHANES cycles using weighted multivariable logistic regression, subgroup analysis, restricted cubic splines (RCS) curve analysis, and causal mediation analysis. Non-high-density lipoprotein to high-density lipoprotein ratio (NHHR) was significantly negatively associated with low bone mass disorders in a fully adjusted model. We found that NHHR exhibited an L-shaped relationship with the prevalence of LBMD, with a negative association when NHHR < 3.38 and no significant association when NHHR > 3.38. So we could manage both disorders through NHHR. Causal mediation analysis demonstrated that NHHR was a partial mediator of the effect of body mass index (BMI) on low bone mass disorders (LBMD), accounting for 2.3% of the total effect. This suggests that part of the effect in weight affecting low bone mass disorders is mediated by the NHHR. This inspires us to utilize NHHR to guide weight management.